Indications
Treatment of Increased Intracranial Pressure (ICP) (see Increased Intracranial Pressure, Increased Intracranial Pressure): intravenous mannitol administration
- Clinical Scenarios
- Fulminant Hepatic Failure with Development of Cerebral Edema (see Fulminant Hepatic Failure, Fulminant Hepatic Failure)
- Large Ischemic Cerebrovascular Accident (CVA) with Development of Cerebral Edema (see Ischemic Cerebrovascular Accident, Ischemic Cerebrovascular Accident)
- Traumatic Brain Injury (TBI) (see Traumatic Brain Injury, Traumatic Brain Injury)
- Administration
- Intravenous Mannitol Administration
Trans-Urethral Resection of the Prostate (TURP) (see Benign Prostatic Hypertrophy, Benign Prostatic Hypertrophy)
- Intravesical Mannitol Administration
Contraindications
Systemic
- Active Intracranial Hemorrhage: except during craniotomy
- Congestive Heart Failure (CHF) (see Congestive Heart Failure, Congestive Heart Failure)
- Pulmonary Edema (see Pulmonary Edema, Pulmonary Edema)
- Severe Dehydration/Hypovolemia (see Hypovolemic Shock, Hypovolemic Shock)
- Severe Renal Disease/Anuria (see Acute Kidney Injury, Acute Kidney Injury and Chronic Kidney Disease, Chronic Kidney Disease)
Genitourinary Irrigation
Pharmacology
Mannitol is an Osmotic Diuretic
- Mannitol Increases the Osmotic Pressure of Glomerular Filtrate, Inhibiting Tubular Resorption of Water/Electrolytes and Increasing Urine Output
- Treatment of Increased Intracranial Pressure (see Increased Intracranial Pressure, Increased Intracranial Pressure)
- Mechanism: unclear
- Mannitol May Decrease Blood Viscosity, Increasing Blood Flow and Oxygen Transport
- Mannitol May Cause Vasoconstriction of the Pial Arteries, Decreasing Cerebral Blood Volume and Intracranial Pressure
- Mannitol May Cause Enhancement of Withdrawal of Water from Brain Parenchyma (and Enhancement of Urinary Water Excretion)
- With Continuous Infusion, Mannitol May Accumulate in the Brain (Resulting in Rebound Increases in Intracranial Pressure): for this reason, intermittent dosing is preferred when treating increased intracranial pressure
- Mechanism: unclear
Pharmacokinetics
- Onset of Action
- Onset of Decrease in Intracranial Pressure: 15-30 min
- Onset of Diuresis: 1-3 hrs
- Duration of Action
- Duration of Decrease in Intracranial Pressure: 1.5-6 hrs
- Elimination Half-Life: 0.25-1.7 hrs
- Elimination Half-Life in the Setting of Renal Failure: 6-36 hrs
Metabolism
- Minimal Hepatic Metabolism to Glycogen
- Approximately 55-87% is Excreted in Urine as Unchanged Drug
Administration
IV (Treatment of Increased Intracranial Pressure) (see Increased Intracranial Pressure, Increased Intracranial Pressure)
- Dose: 0.25-1 g/kg (typically, 50g of 20% solution infused over 30-60 min)
- Repeat q6-8 hrs, as Required
- Dose to Target Desired Serum Osmolality (see Serum Osmolality, Serum Osmolality)
- Hold for Serum Osm >310 mOsm/L
- Alternatively, May Target an Osmolal Gap <18-20
- Hold for Serum Osm >310 mOsm/L
- Infusion Considerations
- Inspect for Crystals Prior to Infusion: may need to resolve by warming
- Do Not Infuse with Packed Red Blood Cells: mannitol may result in crenation or agglutination of red blood cells
- Vesicant (at Concentrations >5%): avoid extravasation
- Management of Extravasation
- Stop Mannitol Infusion and Disconnect (Leaving Cannula in Place)
- Aspirate Extravasated Solution (without Flushing the Line)
- Intradermal or Subcutaneous Hyaluronidase (see Hyaluronidase, Hyaluronidase): using 25-gauge needle and 15 U/mL solution, inject five separate 0.2-0.3 mL injections (total = 1-1.7 mL injected) into the leading edge of extravasation site in clockwise direction
- Apply Dry Cold Compress to Site
- Management of Extravasation
Dose Adjustment
- Hepatic: no dose adjustment is necessary
- Renal: mannitol is contraindicated in the setting of severe renal impairment
Use in Pregnancy (see Pregnancy, Pregnancy)
- Unknown Safety, as Studies Have Not Been Conducted in this Setting
Use in Lactation
- Unknown if Mannitol is Excreted into Breast Milk: caution should be exercised when used in this setting
Drug Interactions
- Aminoglycosides (see Aminoglycosides, Aminoglycosides): systemic mannitol may increase the nephrotoxicity of aminoglycosides (risk: X -> avoid combination)
- Opiates (see Opiates, Opiates): opiates may increase the adverse/toxic effects of diuretics and the therapeutic effects of diuretics (risk: C -> monitor therapy)
Adverse Effects
Renal Adverse Effects
- Acute Kidney Injury (AKI) (see Acute Kidney Injury, Acute Kidney Injury)
- Epidemiology: may occur with high doses
- Physiology: acute renal tubular damage
- Prevention: maintain serum osmolality <320 mOsm/L
- Diuresis
- Clinical
- Hypovolemia
- Electrolyte Depletion
- Clinical
- Elevated Osmolal Gap without Anion Gap Metabolic Acidosis (see Serum Osmolality, Serum Osmolality)
- Pseudohyponatremia (see Hyponatremia, Hyponatremia)
- Physiology: due to mannitol being an osmotically-active solute, water is pulled out of cells, resulting in dilution of serum sodium
Other Adverse Effects
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Adverse Reactions (Frequency not defined):
Cardiovascular: Chest pain, cardiac failure, hypertension, hypotension, local thrombophlebitis, peripheral edema, tachycardia
Central nervous system: Chills, dizziness, headache, seizure
Dermatologic: Bullous rash, urticaria
Endocrine & metabolic: Dehydration (secondary to rapid diuresis), dilutional hyponatremia, electrolyte disturbance (increased osmolar gap), fluid and electrolyte disturbance, hypovolemia (secondary to rapid diuresis), hyperglycemia, hyperkalemia (hyperosmolality-induced), hypernatremia, hypervolemia, metabolic acidosis (dilutional), water intoxication
Gastrointestinal: Nausea, vomiting, xerostomia
Genitourinary: Dysuria
Hypersensitivity: Hypersensitivity reaction
Local: Local pain
Ophthalmic: Blurred vision
Renal: Acute renal failure, tubular necrosis (adult dose: >200 g/day; serum osmolality >320 mOsm/L), polyuria
Respiratory: Pulmonary edema, rhinitis
Miscellaneous: Fever, tissue necrosis
References
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